This conference grant application requests funding to support a comprehensive conference on "Tuberous Sclerosis Complex (TSC): DNA to Human Therapies" scheduled for September 23-26, 2009 in Bloomingdale, IL. The objectives of the Tuberous Sclerosis Complex conference are to: Bring together the TSC research community with other key researchers working on overlapping areas of interest; Discuss the state of our current knowledge about the role of TSC signaling in the central nervous system (CNS) and in other organ systems; Discuss research on the role of the TSC1/2 genes and their protein products in the mTOR signaling pathway in TSC; Discuss the mTORC1and mTORC2 signaling pathway in the pathogenesis of TSC; Discuss if the mTOR signaling pathway answers all of the clinical manifestations of TSC; Discuss the role of TSC signaling in the stress response, nutrient sensing and insulin signaling; Review the results of current and ongoing TSC clinical trials and the need for future clinical trials; Present state of the art clinical research techniques being utilized in TSC;and Identify new areas for therapeutic development to treat manifestations of TSC. The conference has been organized to focus on these objectives, and will feature plenary sessions on the following topics: Opening Session: Overviews of TSC Basic and Clinical Research Session I: Models and Mechanisms of TSC Pathology: Non-CNS Session II: Models and Mechanisms of TSC Pathology: CNS Session III: Brain Development, Epileptogenesis and Neurocognition Session IV: Current and Future Therapeutic Options for TSC and Related Disorders Session V: Does Aberrant mTORC1 Signaling Explain Everything? In addition, a poster session will provide an opportunity for additional conference participants to present their research findings, and breakout discussion groups will allow for discussion among the participants on each of the specific areas covered in the plenary sessions. Travel scholarships will be awarded to young investigators based on review of their submitted abstracts. Since the role of the TSC1/2 genes and their protein products in the mTOR signaling pathway was identified first in Drosophila and then confirmed in mammalian systems, research on TSC has exploded. This research was just emerging at the TSC conference in 2002, supported by the National Institutes of Health, and resulted in the current multicenter clinical trials for both TSC and lymphangioleiomyomatosis (LAM). In 2007, an NIHsupported conference was held in Annapolis, MD. Preliminary data from TSC clinical trials were reported at this meeting, along with significant new information from animal models of TSC. The conference in 2009 will be the first opportunity to present and discussion final results from the TSC clinical trials, additional data from basic research, and discuss plans for new clinical trials utilizing mTOR inhibitors and other drug targets. There are significant research opportunities to be discussed and addressed, and the planned conference will lead to new collaborations and new research avenues for TSC. PUBLIC HEALTH RELEVANCE: Tuberous Sclerosis Complex (TSC) is a public health concern because it equally affects more than 50,000 Americans and more than 1 million individuals of both sexes, all ages, races and ethnic groups. More than 50% of individuals with TSC have moderate to severe disabilities, including epilepsy, intellectual disability, and mental health issues (depression, bipolar disorder, anxiety disorder, autism spectrum disorder) and are not able to live independently. These individuals require lifelong care and depend on services throughout their lives.